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What is the function of the ribosomes?
- RNA protein complexes synthesized in nucleolus and secreted into the cytoplasm. Provide sites for cellular protein synthesis
What is the function of the endoplasmic reticulum? What is the difference between smooth and rough ER?
Network of tubular channels that extend throughout the outer nuclear membrane. Specializes in synthesis and transport of protein and lipid components of most organelles. The difference as Dr. Carlucci tells us between smooth and rough is that rough has ribosomes and smooth does not. I was taught differently but we shall go with that!
What is the function of the golgi complex/apparatus?
Network of smooth membranes and vesicles located near the nucleus. Responsible for processing and packaging proteins onto secretory vesicles that break away from the complex and migrate to various intracellular and extracellular destinations, including plasma membrane. It is like the FedEx delivery guy of the cell.
What is the function of lysosomes?
Saclike structures that originate from the Golgi complex and contain enzymes for digesting most cellular substances to their basic form, such as amino acids, fatty acids and sugars. Cellular injury leads to release of lysosomal enzymes that cause cellular self-destruction.
What is the function of the mitochondria?
- "Powerhouse of the cell"
- Contain metabolic machinery needed for cellular energy metabolism. Enzymes of respiratory chain (electron transport chain) found in inner membrane of mitochondria, generate most of cell's ATP (oxidative phosphorylation). Have a role in osmotic regulation, pH control, calcium homeostasis, and cell signaling.
What is the function of the cytoskeleton?
- "Bone and muscle of the cell"
- Composed of a network of protein filaments, including microtubules and actin filaments (microfilaments) forms cell extensions (microvilli, cilia, flagella)
Describe the different components of this i
- The top portion is called the head.
- It contains the phosphate function group, it is polar and it is hydrophilic. It is considered water soluble friendly
- The bottom portion is called the tail.
- It contains the glycerol and fatty acid chains, it is non polar and it is hydrophobic. It is considered fat soluble friendly
Give two examples of passive transport
Give an example of active transport
Na/K Pumps (Sodium Potassium Pumps)
Why don't the lions want to play poker in the jungle?
Because there are a bunch of cheetahs!!
Don't forget to breathe!
- And laugh a little...
What is the fxn. of the nucleus?
Cell division and control of genetic information
Define total body water (TBW)
- About 60% of body weight in adults is TBW
- The volume of TBW is usually expressed as a percentage of body weight in kilograms
- The rest of the body weight is composed of fat and fat-free solids, particularly bone
Explain the two different types of fluids in the body (ECF, ICF)
- ICF comprises all the fluid within cells, about two-thirds of TBW
- ECF is all the fluid outside the cells, about one-third of TBW and is divided into smaller compartments
What are the two main types of ECF?
- Interstitial fluid (the space between cells and outside the blood vessel) and the intravascular fluid (blood plasma)
- Other ECF compartments include lymph and transcellular fluids (synovial, intestinal and cerebrospinal fluid; sweat; urine; and pleural, peritoneal, pericardial, and intraocular fluids
- fluid movement between plasma and interstitial space.
- Capillary hydrostatic pressure is the primary force for fluid movement out of the arteriolar end of the capillary and into the interstitial space.e
- Excessive accumulation of fluid within the interstitial spaces. The forces favoring fluid movement from the capillaries or lymphatic channels into the tissues are:
- -increased capillary hydrostatic pressure
- -decreased plasma oncotic pressure
- -increased capillary membrane permeability
- -lymphatic channel obstruction
What is the pathophysiology related to venous obstruction?
- Hydrostatic pressure increases as a result of VO, or salt and water retention.
- VO causes hydrostatic pressure to increase behind the obstruction, pushing fluid from the capillaries into the interstitial spaces
- Some causes of VO:
- -Thrombophlebitis (inflammation of veins), hepatic obstruction, tight clothing around the extremities, and prolonged standing
- -CHF, renal failure, cirrhosis of the liver are associated with excessive salt and water retention, which cause plasma volume overload, increased capillary hydrostatic pressure and edema
what are some of the causes of venous obstruction?
- Thrombophlebitis(inflammation of veins)
- Hepatic obstruction
- tight clothing around extremities
- prolonged standing
What is this called?
Learn table 4-4 in book. Won't let me copy it over without the format being way off!
How does sodium contribute to the ECF?
Sodium accounts for 90% of the ECF cations (positively charged ions)
How does Chloride contribute to the ECF?
Chloride is the major anion in the ECF and provides electroneutrality, particularly in relation to sodium
Describe isotonic fluid loss
- IFL causes hypovolemia
- If an individual loses pure plasma or ECF, fluid volume is depleted but the concentration and type of electrolytes and the osmolality remain in the normal range (280-294 mOsm)
What are some of the causes of isotonic fluid loss?
- severe wound drainage
- excessive diaphoresis (sweating)
- Inadequate fluid intake
What are some of the symptoms of hypovolemia?
- Rapid heart rate
- flattened neck veins
- normal or decrease blood pressure
- In severe states:
- Hypovolemic shock
Describe isotonic fluid excess and its causes
- Causes hypervolemia.
- Common causes:
- excessive administration of IV fluids
- Hypersecretion of aldosterone
- the effects of drugs such as cortisone (which causes renal reabsorption of sodium and water)
- Occurs when serum sodium levels exceed 145 mEq/L
- May be caused by retention or infusion of sodium or by decreased intake or increased loss of water
Refers to water deficit but also is commonly used to indicate both sodium and water loss (isotonic or isoosmolar dehydration
- develops when the serum sodium concentration falls below 135 mEq/L
- Occurs when there is a loss of sodium, inadequate intake of sodium, or dilution of sodium by water excess
What causes hyponatremia?
Caused by vomiting, diarrhea, suctioning of GI secretions, and burns or renal losses from use of diuretics. Inadequate intake of dietary sodium is rare
- Caused by compulsive water drinking
- Acute renal failure, severe CHF, and cirrhosis can precipitate water excess during IV infusion of 5% dextrose in water
- Decreased urine formation from renal disease or decreased renal blood flow contributes to water excess
- The overall effect is dilution of the ECF, with water moving to the intracellular space by osmosis.
- AKA potassium deficiency
- Develops when the serum potassium concentration falls below 3.5 mEq/L
What causes hypokalemia
- Reduced intake of potassium
- Increased entry of potassium into cells
- increased losses of body potassium
- Low protein intake and inadequate intake of fruits and vegetables
- alcoholism and anorexia nervosa
- GI and renal disorders
- Diarrhea, intestinal drainage tubes of fistulae and laxative abuse
- Elevation of ECF potassium concentration about 5.5 mEq/L
- because of efficient renal excretion, increases in total body potassium levels are relatively rare
- Acute increases in serum potassium level are handled quickly through increased cellular uptake and renal excretion of K excesses
What causes potassium excess/hyperkalemia?
- Increased intake
- A shift of potassium from cells to the ECF
- decreased renal excretion
- Drugs that decrease renal potassium excretion (ACE inhibitors, angiotensin receptor blockers and aldosterone antagonists)
- Use of stored whole blood and IV boluses of potassium penicillin G or replacement potassium
- Cell trauma, change in cell membrane permeability, acidosis, insulin deficiency, or cell hypoxia
- Burns, massive crushing injuries and extensive surgeries
Describe the purpose of the acid-base balance
- It must be regulated within a narrow range for the body to function normally
- slight changes in amounts of hydrogen can significantly alter biologic processes in cells and tissues
- Hydrogen ion is needed to maintain membrane integrity and the speed of metabolic enzyme reactions
- Most pathologic conditions disturb acid-base balance, producing circumstances possible more harmful than the disease process itself
what does a pH of 7 mean?
The concentration of hydrogen ions in body fluids is very small-approx 0.0000001 mg/L. This number may be expressed as 10 to the -7 is indicated as pH 7.0.
What does pH represent?
- The acidity or alkalinity of a solution. The greater the hydrogen ions, the more acidic the solution and the lower the pH. The lower the hydrogen ions, the more alkaline or basic the solution and the higher the pH
- Normal range in biologic fluids: 7.35-7.45
What is the normal range for pH? What is considered alkalotic and what is considered acidotic?
- Normal: 7.35-7.45
- Alkalotic: Higher than 7.45
- Acidotic: Lower than 7.35
Describe body acids
- They exist in two forms:
- Volatile (can be eliminated as CO2 gas) and nonvolatile (can be eliminated by the kidney)
- Volatile acid is carbonic acid (H2CO3) and is considered a weak acid i.e. it does not release its hydrogen easily.
- In the presence of the enzyme carbonic anhydrase, it readily disassociates into carbon dioxide and water. The CO2 is then eliminated by pulmonary ventilation
- Sulfuric, phosphoric and other organic acids are nonvolatile (strong acids i.e. they readily release their hydrogen)
- Nonvolatile acids are secreted into the urine by the renal tubules
What body part regulates acid-base balance and how?
The distal tubule of the kidney regulates acid-base balance by secreting hydrogen into the urine and reabsorbing bicarbonate
What are the different types of acid-base imbalances?
What is academia/acidosis?
The pH of arterial blood is less than 7.35. A systemic increase in hydrogen ion concentration or loss of base is termed acidosis
What is alkalemia/alkalosis?
The pH of arterial blood is greater than 7.45. A systemic decrease in hydrogen ion concentration or excess of base is termed alkalosis.
How does alkalosis and acidosis occur?
May be caused by metabolic or respiratory processes. See chart made in class for this!
What is metabolic acidosis?
The concentrations of non-carbonic acids increase or bicarbonate is lost from ECF or cannot be regenerated by the kidney. This can occur either quickly, as in lactic acidosis caused by poor perfusion or hypoxemia, or slowly over an extended time, as in renal failure or diabetic ketoacidosis.
What is metabolic alkalosis?
When excessive loss of metabolic acids occurs, bicarbonate concentration increases, causing metabolic alkalosis. When acid loss is caused by vomiting, renal compensation is not very effective because loss of chloride in hydrochloric acid stimulated renal retention of bicarbonate, know an hypochloremic metabolic alkalosis
What is respiratory acidosis?
Occurs when there is alveolar hypoventilation, resulting in an excess of carbon dioxide in the blood (hypercapnia)
What is respiratory alkalosis
Occurs when there is alveolar hyperventilation (deep, rapid respirations) Excessive reduction in plasma carbon dioxide levels (hypocapnia) decrease carbonic acid concentration
Define innate immunity
Also known as natural or native immunity, includes natural barriers (physical, mechanical and biochemical) and inflammation. Innate barriers form the first line of defense at the body's surfaces and are in place at birth to prevent damage by substances in the environment and thwart infection by pathogenic microorganisms.
What happens when our first line of defense (body's surface) is compromised in the presence of pathogens?
If surface barriers are breached, the second line of defense, the inflammatory response, is activated to protect the body from further injury, prevent infection of the injured tissue and promote healing. The IR is a rapid citation of biochemical and cellular mechanisms that are relatively non-specific, with similar responses being initiated against a wide variety of causes of tissue damage.
What is considered our third line of defense with innate immunity?
- Also known as acquired or specific immunity
- It is induced in a relatively slower and more specific process and targets particular invading microorganisms for the purpose of eradicating them. Adaptive memory also involves memory, which results in a more rapid response during future exposure to the same microorganism.
What are the physical barriers of the human body and how do they function?
- They cover the external parts of the human body
- They are composed of tightly associated epithelial cells of the skin and of the linings of the GI, genitourinary and respiratory tracts.
- When pathogens attempt the penetrate the barrier, they may be removed by mechanical means-sloughed off with dead skin cells, expelled by coughing or sneezing, vomited from the stomach or flushed from the urinary tract by urine.
- Epithelial cells of the upper respiratory tract also produce mucus and hair-like cilia that trap and move pathogens upwards and outwards.
- The low temperature, such as of the skin and stomach, generally inhibit microorganisms
Describe normal flora
- A spectrum of nonpathogenic microorganisms that reside on body surfaces.
- Composed mostly of bacteria and occasionally fungi that is unique to the location it resides.
Where are normal flora found?
- Mucous membranes of the eyes, upper and lower GI tracts, urethra and vagina
An example of normal flora can be given for the colon:
- At birth, the lower gut is relatively sterile, but colonization with bacteria begins quickly, with the number, diversity and concentration increasing throughout life
- The environment of the intestine provides the needed temperature and nutrients for the growth of many bacterial species. To the benefit of humans, many of these microorganisms help digest fatty acids, large polysaccharide and other dietary substances; produce biotin and vitamin K; and assist in the absorption of various ions, such as calcium, iron and magnesium
How does the normal flora function to protect against pathogens?
- Compete with pathogens for nutrients and block attachment to epithelium
- Produce chemicals (ammonia, phenols and insoles and other toxic materials) and toxic proteins (bacteriocins) that inhibit colonization by pathogenic microorganisms
- The normal flora of the gut help train the adaptive immune system by inducing growth of gut-associated lymphoid tissue and the development of both local and systemic adaptive immune systems.
What is the effect of prolonged treatment with antibiotics?
They can alter the normal flora, decreasing its protective activity and lead to an overgrowth of pathogenic microorganisms such as the yeast Candida albicans or the bacteria Clostridium difficult.
What is the function of the bacterium Lactobacillus?
- It is a major constituent of the nomad vaginal flora in healthy women
- This microorganism produces chemicals that help prevent infections of the vagina and urinary tract by other baxter and yeast
- Diminished colonization with lactobacilli (as a result of prolonged antibiotic treatment) increases the risk for urologic or vaginal infections, such as vaginosis
What does it mean for the normal flora to be opportunistic microorganisms?
- Opportunistic microorganisms can cause disease if the individual's defenses are compromised.
- These organisms are normally controlled by the innate and acquired immune systems and contribute to our defenses.
Give an example of an opportunistic microorganism
Pseudomonas aeruginosa is a member of the normal flora of the skin and produces a toxin that protects against infections with staphylococcal and other bacteria. Howeever, severe burns compromise the integrity of the skin and may lead to life-threatening systemic pseudomonal infections
- The innate immune system is programmed to respond to damage to the body, whether the damaged tissue is septic or sterile
- That response rapidly initiated an interactive system of humoral and cellular systems called inflammation.
- It is the first response to injury
- Occurs is tissues with a blood supply
- Activated rapidly (within seconds) after damage occurs
- Depends on the activity of both cellular and chemical components
- Nonspecific meaning that is takes place in approx. the same way regardless of the type of stimulus or whether exposure to the same stimulus has occurred in the past
What are the symptoms of inflammation?
- Redness (erythema)
- loss of function
What is the process of inflammation?
- 1. Vasodilation (increased size of blood vessels) which causes slower blood velocity and increases blood flow to the injured site
- 2. Increased vascular permeability (the blood vessels become porous from contraction of endothelial cells) and leakage of fluid out of the vessel (exudation) causing swelling (edema) at the site of injure; as plasma moves outward, blood in the microcirculation becomes more viscous and flows more slowly, and the increases blood flow and increasing concentration of red cells at the site of inflammation cause locally increases redness (erythema) and warmth
- 3. White blood cell adherence to the inner walls of vessels and their migration through enlarged junctions between the endothelial cells lining the vessels into the surrounding tissue
What are the benefits of inflammation?
1. Prevents infection and further damage by contaminating microorganism through the influx of plasma to dilute toxins produced by bacteria and released from dying cells, the influx and activation of plasma protein systems that help contain and destroy bacteria
What happens to fluid and debris that accumulate at an inflamed site?
They are drained by lymphatic vessels
What are the three plasma protein systems?
- Complement system
- Clotting system
- Kinin system
What are the similarities of the plasma protein systems?
- Each has a role in inflammation
- Consists of multiple proteins in the blood
- Normally in inactive forms; several are enzymes that circulate in inactive forms as proenzymes
- Each contains a few proteins that can be activated during inflammation
- Results in sequential activation of other components of the system, leading to a biologic fxn. that helps protects the helps protect the individual.
What is the complement system?
- Consists of a large number of proteins (sometimes called complement factors) that together constitute about 10% of the total circulating serum protein
- It is extremely important because activation produces factors that can destroy pathogens directly or can activate or increase the activity of many other components of the inflammatory and adaptive immune response
- Factors produced during activation of the complement system are among the body's most potent defenders against bacterial infection
- Most important fxn. is activation of C3 and C5, which results in a variety of molecules that are 1) opsonins, 2) chemotactic factors or 3) anapylatoxins
What are opsonins?
They coat the surface of bacteria and increase their susceptibility to being phagocytized and killed by inflammatory cells, such as neutrophils and macrophages
What are chemotactic factors?
Diffuse from a site of inflammation and attract phagocytic cells to that site
What are anaphylatoxins?
They induce rapid degranulation of mast cells (i.e. release of histamine that induces vasodilation and increased capillary permeability)
Describe the clotting system
an be activated by the tissue factor (extrinsic) pathway and the contact activation (intrinsic) pathway. All routes of clotting initiation lead to activation of factor X and thrombin. Thrombin is an enzyme that proteolytically activates fibrinogen to form fibrin and small fibrinopeptides (FPs). Fibrin polymerizes to form a clot, and the FPs are highly active as chemotactic factors and causing increased vascular permeability. The XIIa produced by the clotting system can also be activated by kallikrein of the kinin system
Describe the kinin system
Prekallikrein is enzymatically converted to kininogen, which activates bradykinin. Bradykinin functions similar to histamine and increases vascular permeability. Bradykinin can also stimulate nerve endings to cause pain. TF, tissue factor; FPs, Fibrinopeptides.
Plasma protein systems (image)
What is the clotting system?
a group of plasma proteins that, when activated sequentially, form a blood clot.
What is the fxn. of blood clots?
A blood clot is a meshwork of protein (fibrin) strands that stabilizes the platelet plug and traps other cells, such as erythrocytes, phagocytes, and microorganisms.11 Clots (1) plug damaged vessels and stop bleeding, (2) trap microorganisms and prevent their spread to adjacent tissues, and (3) provide a framework for future repair and healing.
Describe the kinin system
- Interacts closely with the coagulation system.
- The final product of the kinin system is a small-molecular-weight molecule, bradykinin
What is bradykinin?
- it is produced from a larger precursor molecule, kininogen. Bradykinin causes dilation of blood vessels, acts with prostaglandins to induce pain, causes smooth muscle cell contraction, and increases vascular permeability
- Final product of the kinin system
Control and interaction of plasma protein systems
- The three plasma protein systems are highly interactive so that activation of one results in production of a large number of very potent, biologically active substances that further activate the other systems. Very tight regulation of these processes is essential for the following two reasons.
- 1. The inflammatory process is critical for an individual's survival; thus efficient activation must be guaranteed regardless of the cause of tissue injury. Interaction among the plasma systems results in activation of the entire inflammatory response regardless of which system is activated initially.
- 2. The biochemical mediators generated during these processes are so potent and potentially detrimental to the individual that their actions must be strictly confined to injured or infected tissues.
Misc. info about clots
The formation of clots also activates a fibrinolytic system that is designed to limit the size of the clot and remove the clot after bleeding has ceased. Thrombin of the clotting system activates plasminogen in the blood to form the enzyme plasmin. The primary activity of plasmin is to degrade fibrin polymers in clots.
What are interleukins
- They are produced predominantly by macrophages and lymphocytes in response to stimulation of PRRs or by other cytokines. More than 30 interleukins have been identified. Their effects include the following:
- 1. Alteration of adhesion molecule expression on many types of cells
- 2. Attraction of leukocytes to a site of inflammation (chemotaxis)
- 3. Induction of proliferation and maturation of leukocytes in the bone marrow
- 4. General enhancement or suppression of inflammation.
Is an endogenous pyrogen (i.e. fever-causing cytokine) that reacts with receptors on cells of the hypothalamus and affects the body's thermostat, resulting in fever
What is degranulation and what is it's fxn?
- The release of the contents of mast cell granules
- In response to a stimulus, biologically active molecules are released from the mast cell granules within seconds and exert their effects immediately. These molecules include histamine and chemotactic factors.
What is histamine and what is its function?
small-molecular-weight molecule with potent effects on many other cells, particularly those that control the circulation. Histamine, along with serotonin (found in many cells, but not human mast cells), is called a vasoactive amine. These molecules cause temporary, rapid constriction of smooth muscle and dilation of the postcapillary venules, which results in increased blood flow into the microcirculation. Histamine also causes increased vascular permeability resulting from retraction of endothelial cells lining the capillaries and increased adherence of leukocytes to the endothelium.
What are the chemotactic factors contained in mast cell granules?
- Neutrophil chemotactic factor
- Eosiniophil chemotactic factor of anaphylaxis
What is the fxn. of prostaglandins?
cause increased vascular permeability, neutrophil chemotaxis, and pain by direct effects on nerves.
What are some characteristics of the vessel walls?
consist of a layer of endothelial cells that adhere to an underlying matrix of connective tissue. The matrix contains a variety of proteins, including collagen, fibronectin, and laminins. Circulating cells and platelets and components of plasma protein systems continually contact endothelial cells lining the blood vessels.
What is the fxn. of endothelial cells?
regulate circulating components of the inflammatory system and maintain normal blood flow by preventing spontaneous activation of platelets and members of the clotting system. Endothelial cells produce nitric oxide (NO) from arginine and prostacyclin (PGI2) from arachidonic acid. Both NO and PGI2 maintain blood flow and pressure and inhibit platelet activation. PGI2 and NO are synergistic. NO is released continually to relax vascular smooth muscle and suppress the effects of low levels of cytokines, thus maintaining vascular tone. PGI2 production varies a great deal and is increased when additional regulation is needed.
What happens when damage occurs to the endothelial cell lining of the vessel?
It exposes the subendothelial connective tissue matrix, which is prothrombogenic and initiates platelet activation and formation of clots
What are platelets and what is their fxn?
cytoplasmic fragments formed from megakaryocytes. They circulate in the bloodstream until vascular injury occurs. After injury, platelets are activated by many products of tissue destruction and inflammation, including collagen, thrombin, and platelet-activating factor.26 Activation results in (1) their interaction with components of the coagulation cascade to stop bleeding11 and (2) degranulation, releasing biochemical mediators such as serotonin, which has vascular effects similar to those of histamine. Platelets also release growth factors that promote wound healing.
Describe the neutrophil and its functions
The neutrophil, or polymorphonuclear neutrophil (PMN), is a member of the granulocytic series of white blood cells and is named for the characteristic staining pattern of its granules as well as its multilobed nucleus. Neutrophils are the predominant phagocytes in the early inflammatory site, arriving within 6 to 12 hours after the initial injury.
What is a monocyte?
The immature form of the white blood cells in the blood
What is a macrophage?
A mature cell in the tissues
What is the process of phagocytosis (descriptive version)
Take a deep breath!
The process that results in phagocytosis is characterized by three interrelated steps: adherence and diapedesis, tissue invasion by chemotaxis, and phagocytosis. A, Adherence, margination, diapedesis, and chemotaxis. The primary phagocyte in the blood is the neutrophil, which usually moves freely within the vessel (1). At sites of inflammation, the neutrophil progressively develops increased adherence to the endothelium, leading to accumulation along the vessel wall (margination or pavementing) (2). At sites of endothelial cell retraction the neutrophil exits the blood by means of diapedesis (3)Chemotaxis. In the tissues, the neutrophil detects chemotactic factor gradients through surface receptors (1) and migrates towards higher concentrations of the factors (2). The high concentration of chemotactic factors at the site of inflammation immobilizes the neutrophil (3)B, Specific receptors for recognition and attachment. C, Phagocytosis. Opsonized microorganisms bind to the surface of a phagocyte through specific receptors (1). The microorganism is ingested into a phagocytic vacuole, or phagosome (2). Lysosomes fuse with the phagosome, resulting in the formation of a phagolysosome (3). During this process the microorganism is exposed to products of the lysosomes, including a variety of enzymes and products of the hexose-monophosphate shunt (e.g., H2O2, O2−). The microorganism is killed and digested (4)Ab, Antibody; AbR, antibody receptor; C3b, complement component C3b; C3bR, complement C3b receptor; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor.
Process of phagocytosis (image)
What is phagocytosis (brief version)?
the process by which a cell ingests and disposes of foreign material, including microorganisms. Cells that perform this process are called phagocytes. The two most important phagocytes are neutrophils and macrophages
Describe the symptoms of acute inflammation
- Results from vascular changes and the subsequent leakage of circulating components into the tissue
Different types of exudate
The exudate of inflammation varies in composition, depending on the stage of the inflammatory response and, to some extent, the injurious stimulus. In early or mild inflammation, the exudate is watery (serous exudate) with very few plasma proteins or leukocytes. An example of serous exudate is the fluid in a blister. In more severe or advanced inflammation, the exudate may be thick and clotted (fibrinous exudate), such as in the lungs of individuals with pneumonia. If a large number of leukocytes accumulate, as in persistent bacterial infections, the exudate consists of pus and is called a purulent (suppurative) exudate. Purulent exudate is characteristic of walled-off lesions (cysts or abscesses). If bleeding occurs, the exudate is filled with erythrocytes and is described as a hemorrhagic exudate.
What is leukocytosis?
- An increase in the number of circulating white blood cells (greeter than 11,000/ml3 in adults)
- During many infections, leukocytosis may be accompanied by a left shift in the ration of immature to mature neutrophils
What is chronic inflammation?
- Superficially, the difference between acute and chronic inflammation is duration; chronic inflammation lasts 2 weeks or longer, regardless of cause. Chronic inflammation is sometimes preceded by an unsuccessful acute inflammatory response.
- For example, if bacterial contamination or foreign objects (e.g., dirt, wood splinter, and glass) persist in a wound, an acute response may be prolonged
Describe wound healing
Wound healing involves processes that (1) fill in, (2) seal, and (3) shrink the wound. These characteristics of healing vary in importance and duration among different types of wounds. A clean incision, such as a paper cut or a sutured surgical wound, heals primarily through the process of collagen synthesis. Because this type of wound has minimal tissue loss and close apposition of the wound edges, very little sealing (epithelialization) and shrinkage (contraction) are required.
What is primary intention?
Wounds that heal under conditions of minimal tissue loss are said to heal by primary intention
What is secondary intention?
Healing of an open wound, such as a stage IV pressure ulcer (decubitus ulcer), requires a great deal of tissue replacement so that epithelialization, scar formation, and contraction take longer and healing occurs through secondary intention
What are the different phases of wound healing?
What is granulation tissue?
grows into the wound from surrounding healthy connective tissue. Granulation tissue is filled with new capillaries (angiogenesis) derived from capillaries in the surrounding tissue, giving the granulation tissue a red, granular appearance.
Describe dysfunctional wound healing
Dysfunctional wound healing and impaired epithelialization may occur during any phase of the healing process. The cause of dysfunctional wound healing includes ischemia, excessive bleeding, excessive fibrin deposition, a predisposing disorder such as diabetes mellitus, wound infection, inadequate nutrients, numerous drugs, and tobacco smoke
What is the problem with oxygen-deprived (ischemic) tissues?
They are susceptible to infection, which prolongs inflammation and delays healing. Ischemia reduces energy production and impairs collagen synthesis and the tensile strength of regenerating connective tissue.
Persons with diabetes are at risk for prolonged wound healing.
Why is optimal nutrition important during all phases of healing?
Because metabolic needs increase
What can delay wound healing?
Medications, including antineoplastic (anticancer) agents, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids, delay wound healing.
What are antigens?
The immune system is capable of identifying substances that are foreign, or nonself. In general, substances that react with molecules of the immune system (antibodies, receptors on B and T cells) are called antigens. Antigens are on infectious agents (e.g., viruses, bacteria, fungi, or parasites), on noninfectious substances from the environment (e.g., pollens, foods, or bee venoms), or on drugs, vaccines, transfusions, and transplanted tissues
Immunoglobulins (Ig or antibodies)
- The term generally used for all antibodies
- Products of the adaptive immune response
- A type of serum protein
What do B cells produce?
Variations in immune system ability
the genetic makeup of the individual can play a critical role in the immune system's ability to respond to many antigens. Some individuals appear to be unable to respond to immunization with a particular antigen, whereas they respond well to other antigens. For instance, a small percentage of the population may fail to produce a measurable immune response to a common vaccine, despite multiple injections. An individual's immune response can also be affected by age, nutritional status, genetic background, and reproductive status, as well as exposure to traumatic injury, concurrent disease, or the use of immunosuppressive medications.
What is the most abundant immunoglobulin?
- constituting 80% to 85% of the immunoglobulins in the blood and accounting for most of the protective activity against infections. As a result of selective transport across the placenta, maternal IgG is the major class of antibody found in blood of the fetus and newborn.
- IgA1 is found predominantly in the blood
- IgA2 is the predominant class found in body secretions
- the largest Ig and usually exists as a pentamer that is stabilized by a J chain. It is the first antibody produced during the initial, or primary response to antigens
- IgM is synthesized early in neonatal life, and its synthesis may be increased as a response to infection in utero
Describe monoclonal antibodies
They are produced in the laboratory from one B cell that has been cloned; thus all the antibody is of the same class, specificity, and function. The advantages of monoclonal antibodies are that (1) a single antibody of known antigenic specificity is generated rather than a mixture of different antibodies; (2) monoclonal antibodies have a single, constant binding affinity; (3) monoclonal antibodies can be diluted to a constant titer (concentration in fluid) because the actual antibody concentration is known; and (4) the antibody can be easily purified. Thus, a highly concentrated antibody with optimal function has been used to develop extremely specific and sensitive laboratory tests (e.g., home and laboratory pregnancy tests) and therapies (e.g., for certain infectious diseases or several experimental therapies for cancer).
Toxins in regards to antibodies
Some bacteria secrete toxins that harm individuals. For instance, specific bacterial toxins cause the symptoms of tetanus or diphtheria. Most toxins are proteins that bind to surface molecules on cells and damage those cells. Protective antibodies can bind to the toxins, prevent their interaction with host cells, and neutralize their biologic effects. Detection of the presence of an antibody response against a specific toxin (antibodies referred to as antitoxins) can aid in the diagnosis of diseases. For example, laboratory tests that detect antistreptolysin O can be useful in diagnosing group A streptococcal infections.
- Special class of antibody that protects the individual from infection with large parasites
- When IgE is produced against relatively innocuous environmental antigens, it is also the primary cause of common allergies (hay fever, dust allergies, bee stings)
What are major histocompatibility complex molecules?
They are glycoproteins found on the surface of all human cells except red blood cells
How could you say that developed countries have a better chance of preventing diseases? Sorry this is a poorly worded question but you will understand what I mean on the answer!
- Developed countries have:
- sanitary living conditions
- Clean water
- Uncontaminated food
- Antimicrobial medications
Break down the types of deaths in the United States (another poorly worded questions)
In the United States, heart disease and malignancies greatly surpass infectious disease as major causes of death.1 However, many deaths related to cancer are the result of secondary infections because the immune system can be severely depressed both by the cancer itself and by many of the treatments used to fight the cancer. Influenza/pneumonia (eighth leading cause) and sepsis (eleventh leading cause) accounted for more than 89,000 deaths (3.6% of the total number of deaths).
What have vaccinations done to infectious diseases?
nfectious disease remains a significant threat to life in many parts of the world, including India, Africa, and Southeast Asia, although the advent of sanitary living conditions, clean water, uncontaminated food, vaccinations, and antimicrobial medications has improved the health of many. As a result of these initiatives smallpox has been eradicated from the globe (the last reported case was in 1975 in Somalia); measles has nearly been eliminated in the Western Hemisphere; and many diseases, such as measles (decreased by 78% since 2000)2 and polio (declined by more than 99% since 1988),3 are decreasing in prevalence worldwide.
How have infectious diseases "fought" against antibiotics?
Although vaccines and antimicrobials have altered the prevalence of some infectious diseases, mutant strains of bacteria and viruses have emerged with resistance to protection provided by drug therapy. The emergence of new diseases—such as West Nile virus, severe acute respiratory syndrome (SARS), Lyme disease, and Hantavirus—and the development of drug-resistant tuberculosis are examples of the current intense challenges in the struggle to prevent and control infectious disease. Some tropical diseases are emerging for the first time in the United States
How have infectious diseases "fought" against antibiotics?
Although vaccines and antimicrobials have altered the prevalence of some infectious diseases, mutant strains of bacteria and viruses have emerged with resistance to protection provided by drug therapy. The emergence of new diseases—such as West Nile virus, severe acute respiratory syndrome (SARS), Lyme disease, and Hantavirus—and the development of drug-resistant tuberculosis are examples of the current intense challenges in the struggle to prevent and control infectious disease. Some tropical diseases are emerging for the first time in the United States
Health Alert: Increase in United States of "Tropical Diseases"
This is length but there wasn't really a way to break it down-sorry!
- There was a time when vector-borne tropical diseases were contained, particularly by active insect control programs. Recently, diseases such as malaria, dengue hemorrhagic fever, yellow fever, and African trypanosomiasis are reemerging in areas of Africa and the Americas where they had been eliminated or unreported. Although in recent history the United States has been relatively free of most of these diseases, it should not be forgotten that in 1793 a yellow fever outbreak in Philadelphia killed 2000 of the city's 55,000 inhabitants and forced the U.S. government to abandon the city until the outbreak ceased. The conditions necessary for resurgence of outbreaks still exist; the necessary vectors are still available, the population density and socioeconomic conditions are favorable, and the population generally does not have existing immunity to these disease-causing agents. The effects of global warming on the spread of these diseases can only be speculated.
- In early 2010 the CDC reported the results of their study of 28 cases of locally-acquired dengue hemorrhagic fever in Key West, Florida. The dengue virus is transmitted by mosquitoes and yearly causes 50 to 100 million infections worldwide and 25,000 deaths. These were the first cases of locally acquired disease in the United States since 1945. A survey of mosquito breeding pools discovered the virus in at least two sites. The report surmised, while acknowledging that other factors could play a role, the increased incidence of dengue fever resulted from increased travel to localities where the disease was endemic, return of infected travelers, and transmission of the virus to the vector pool. The development of dengue vaccines is in progress.
Another lengthy section, but I think this will help when trying to understand the relationship between microorganisms and humans!
For many microorganisms, the human body is a very hospitable site to grow and flourish. The microorganisms are provided with nutrients and appropriate conditions of temperature and humidity. In many cases a mutual relationship exists in which humans and the microorganisms benefit (Box 7-1). For instance, the human gut is colonized by a large variety of microorganisms that make up normal human flora. The normal flora of different body areas are summarized in Table 7-1. Bacteria in the GI tract are provided with nutrients from ingested food, and in exchange they produce (1) enzymes that facilitate the digestion and utilization of many molecules in the human diet, (2) antibacterial factors that prevent colonization by pathogenic microorganisms (see Chapter 5), and (3) usable metabolites (e.g., vitamin K, B vitamins). This relationship normally is maintained through the physical integrity of the skin and mucosal epithelium and other mechanisms that guarantee that the immune and inflammatory systems do not attack these symbiotes. If those systems are compromised, many microorganisms will leave their normal sites and cause infection. Individuals with deficiencies in their immune system become easily infected with opportunistic microorganisms—those that normally would not cause disease but seize the opportunity provided by the person's decreased immune or inflammatory responses.
Ability of an agent to produce disease
Capacity of a pathogen to cause severe disease
Pathogens that directly cause tissue damage
- Streptococcus pyogenes causes tonsillitis
- Escherchia coli causes gram-negative sepsis
- Pseudomonas aeruginosa causes wound infection
- Herpes simplex virus causes cold sores
Just a fact
Gram stain and acid-fast stain are important for differentiating gram-positive or gram-negative types of bacteria.
The presence of bacteria in the blood
The growth of bacteria in the blood
What is the difference between bacteremia and septicemia?
Bacteremia is the presence of bacteria in the blood, whereas septicemia is growth of bacteria in the blood
What are mycoses
Disease caused by fungi are mycoses. They can be superficial, deep or opportunistic
Where is candida albicans normally found in the body?
- GI Tract
- Changes in the pH and use of antibiotics that destroy bacteria that normally inhibit Candida growth permit rapid proliferation and overgrowth, which can lead to superficial or deep infection
Why have multiple antibiotic-resistant microorganisms appeared?
Lack of compliance concerning the necessity of completing the therapeutic regimen with antibiotics allows the selective resurgence of microorganisms that are more relatively resistant to the antibiotic. Overuse of antibiotics can lead to the destruction of the normal flora, allowing the selective overgrowth of antibiotic-resistant strains or pathogens that had previously been controlled. For example, after treatment with the antibiotic clindamycin, the normal intestinal flora can become compromised, allowing the overgrowth of Clostridium difficile and the development of pseudomembranous colitis (a bacterial infection of the intestines). C. difficle infections are often acquired in hospitals or other healthcare institutions with a long-term patient population and the number of deaths is rising steadily; reported deaths rose from 793 in 1999 to 6372 deaths in 2007, with 92% of the deaths occurring in individuals age 65 years or older.1
Health Alert: THe continued rise of antibiotic-resistant microorganisms
Another length one but important!
- The existence of antibiotic-resistant pathogenic bacteria was observed soon after the advent of antibiotic therapy during World War II. In most cases alternative antibiotics were readily available. Many common pathogenic bacteria and yeast have since developed resistance to multiple antibiotics: Mycobacterium tuberculosis, Enterococcus, Clostridium difficile, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida, and others. A major example has been Staphylococcus aureus. S. aureus is part of the normal bacterial flora present in healthy individuals; about 30% of healthy individuals have asymptomatic colonization in the nostrils. Penicillin-resistant S. aureus was reported in the 1950s and methicillin-resistant S. aureus (MRSA) organisms were reported in the early 1960s. Currently, the prevalence of MRSA with resistance to other antibiotics (multidrug resistant) is increasing. In the past MRSA was observed primarily in hospitals and nursing homes in persons whose defenses had been compromised. Now it is becoming the primary microorganism found in community-acquired infections, primarily skin infections such as cellulitis and abscesses, of healthy individuals. Community-acquired MRSA has not yet developed multiple antibiotic resistance.
- The situation may be about to become considerably worse. Very recently strains of multiple antibiotic-resistant Neisseria gonorrhoeae have emerged. The incidence of gonorrhea has been relatively stable in the United States with more than 260,000 new cases of gonorrhea reported for 2009, which may be considerably underestimated. In 2007 27% of isolates were resistant to a large variety of antibiotics, and the CDC had recommended cephalosporins as the only class of antibiotics for treating gonorrhea. Recently investigators from Australia and England have identified strains that are resistant to cefiximine and ceftriaxone, widely used cephalosporins.
What are vaccines?
biologic preparations of weakened or dead pathogens that when administered stimulate production of antibodies or cellular immunity against the pathogen without causing disease.
What is the purpose of vaccinations?
to induce long-lasting protective immune responses under conditions that will not result in disease in a healthy recipient of the vaccine. The primary immune response from vaccination is generally short lived; therefore booster injections are used to push the immune response through multiple secondary responses that result in large numbers of memory cells and sustained protective levels of antibody or T cells, or both.
What have mass vaccinations done for the world's health?
Mass vaccination programs have been tremendously successful and have led to major changes in the health of the world's population. In the early 1950s an estimated 50 million cases of smallpox occurred each year, with about 15 million deaths. The World Health Organization (WHO) conducted a smallpox immunization campaign from 1967 to 1977 that resulted in the global eradication of smallpox by 1979. Many vaccines are used in the United States to protect against pathogens.
What is an attenuated virus?
- Used for vaccinations
- Most vaccines against viral infections (measles, mumps, rubella, varicella (chicken pox)) contain live viruses that are weakened, aka attenuated viruses
- They express appropriate antigens but they only establish a limited and easily controlled infection
How has the pertussis vaccine changed?
- aka Whooping cough vaccine
- It has been changed from a killed whole-cell vaccine to cellular extract (acellular) vaccine that contains the pertussis toxoid and additional bacterial antigens. This change has dramatically reduced adverse side effects (fever, local inflammatory reactions, and others).
Combining vaccines/resistance to vaccinations
- With so many available vaccines there has been an effort to combine vaccines in order to minimize the number of required injections. One of the first licensed vaccine mixtures was DPT, which now usually contains diphtheria (D) and tetanus (T) toxoids and acellular pertussis vaccine (aP). More recent mixtures include DTaP with inactivated poliovirus, either with Hib conjugate to tetanus toxoid or with hepatitis B vaccine.
- A common problem is compliance of the susceptible population in vaccination programs. Even with successful development of a vaccine, however, a certain percentage of the population will be genetically unresponsive to vaccination and therefore will not produce a protective immune response. With most vaccines, the percentage of unresponsive individuals is low, and they will benefit from successful immunization of the rest of the population. Depending on the microorganism, a certain percentage of the population (usually about 85%) should be immunized in order to achieve protection of the total population. This is referred to as herd immunity. If this level of immunization is not achieved, outbreaks of infection can occur. For instance, an effective measles (rubeola) vaccine was made available in 1963 and resulted in a dramatic decrease in the number of measles cases. Many parents became complacent and did not obtain measles vaccination for their preschool children. As a result, a large increase in the number of cases and deaths in 1989 and 1990 occurred, which initiated a reemphasis on complete immunization before children could start school. More recently resistance to immunization with measles has increased, and in early 2008 the number of measles cases in the United States increased by about fourfold. In several European countries immunization programs have been disrupted by antivaccine groups. As a result the incidence of pertussis (whooping cough) increased by 10 to 100 times compared with neighboring countries that maintained a high incidence of immunization.
- The reluctance to vaccinate has generally been based on potential vaccine dangers. As with any medicine, complications can arise. In the case of vaccines, these include pain and redness at the injection site, fever, allergic reactions to vaccine ingredients, infection associated with attenuated viruses in immune-deficient individuals, and others. Some dangers do exist, although extremely rarely. For instance, a rotavirus vaccine approved more than a decade ago was found to increase the risk for a life-threatening bowel obstruction resulting from twisting of the intestines, and the vaccine was recalled. More commonly the reluctance is based on inadequate information. A commonly discussed fear is related to the presence of the preservative thimerosal in vaccines. Thimerosal is a mercury-containing compound that has been used as a preservative since the 1930s. Although no cases of mercury toxicity have been reported secondary to vaccination, thimerosal was removed from all vaccines in 2001, with the exception of some inactivated influenza vaccines.In 2003 groups in northern Nigeria claimed that the oral polio vaccine was unsafe and were tainted with antifertility drugs (estradiol), HIV, and cancer-causing agents. The reasoning appeared to be secondary to mounting distrust of Western nations because of conflicts in the Middle East. The effect was suspension of polio immunization for almost 1 year in two states and reduction of immunization in three other states. The incidence of polio rose dramatically and more than 27,000 cases of paralysis resulted. By 2006 Nigeria accounted for 51% of the global polio cases, and this region acted as a reservoir for the dissemination of polio to previously polio-free areas in neighboring countries. After renewal of immunization programs the number of cases of polio in Nigeria has since dropped by more than 90% to only 388 new cases in 2009
What is HIV
Acquired immunodeficiency syndrome is a secondary immune deficiency that develops in response to viral infection. The human immunodeficiency virus (HIV) infects and destroys the Th cell, which is necessary for the development of both plasma cells and cytotoxic T cells. Therefore HIV suppresses the immune response against itself and secondarily creates a generalized immune deficiency by suppressing the development of immune responses against other pathogens and opportunistic microorganisms, leading to the development of acquired immunodeficiency syndrome (AIDS).
What is the epidemiology of AIDS
HIV is a blood-borne pathogen with the typical routes of transmission: blood or blood products, intravenous drug abuse, both heterosexual and homosexual activity, and maternal-child transmission before or during birth. Although the disease first gained attention in the United States related to sexual transmission between males, the most common route worldwide is through heterosexual activity. Worldwide, women constitute more than half of those living with HIV/AIDS. In the United States, as in the rest of the world, the predominant means of transmission to women is through heterosexual contact, and the incidence of HIV/AIDS is increasing faster in women than men, particularly in the adolescent age groups. Hundreds of thousands of cases of HIV/AIDS have been reported in children who contracted the virus from their mothers across the placenta, through contact with infected blood during delivery, or through the milk during breast-feeding.
What is the pathogenesis of AIDS
HIV is a member of a family of viruses called retroviruses, which carry genetic information in the form of RNA rather than DNA. Retroviruses use a viral enzyme, reverse transcriptase, to convert RNA into double-stranded DNA. Using a second viral enzyme, an integrase, the new DNA is inserted into the infected cell's genetic material, where it may remain dormant. If the cell is activated, translation of the viral information may be initiated, resulting in the formation of new virions, lysis and death of the infected cell, and shedding of infectious HIV particles. During that process the viral protease is essential in processing proteins needed from the viral internal structure (capsid). If, however, the cell remains relatively dormant, the viral genetic material may remain latent for years and is probably present for the life of the individual.
What is the classification of approved AIDS medications?
- Approved AIDS medications are classifies by mechanism of action.
- The current regimen for treatment of HIV infection is a combination of drugs, termed highly active antiretroviral therapy (HAART). HAART protocols require a combination of three synergist drugs from two different classes. The clinical benefits of HAART are profound. Death from AIDS-related diseases has been reduced significantly since the introduction of HAART. However, resistant variants to these drugs have been identified. Drug therapy for AIDS is not curative because HIV incorporates into the genetic material of the host and may never be removed by antimicrobial therapy. Therefore drug administration to control the virus may have to continue for the lifetime of the individual. Additionally, HIV may persist in regions where the antiviral drugs are not as effective, such as the CNS.
- Vaccine development is probably the most effective means of preventing HIV infection and may be useful in treating preexisting
Allergy, autoimmunity, and alloimmunity are classified as hypersensitivity reactionsHypersensitivity is an altered immunologic response to an antigen that results in disease or damage to the individual. Allergy, autoimmunity, and alloimmunity (also termed isoimmunity) can be most easily understood in relationship to the source of the antigen against which the hypersensitivity response is directed
Disturbance in the immunologic tolerance of self-antigens
Define immediate hypersensitivity reactions
Reactions that occur within minutes to a few hours after exposure to antigen
Define delayed hypersensitivity reactions
May take several hours to appear and are at maximal severity days after reexposure to the antigen
What is the most rapid and severe immediate hypersensitivity reaction?
- Anaphylaxis occurs within minutes of reexposure to the antigen and can be either systemic (generalized) or cutaneous (localized). Symptoms of systemic anaphylaxis include pruritus, erythema, vomiting, abdominal cramps, diarrhea, and breathing difficulties. Severe anaphylactic reactions may include contraction of bronchial smooth muscle, edema of the throat, breathing difficulties, decreased blood pressure, shock, and death. An example of systemic anaphylaxis is an allergic reaction to bee stings. Cutaneous anaphylaxis results in local symptoms, such as pain, swelling, and redness, which occur at the site of exposure to an antigen (e.g., a painful local reaction to an injected vaccine or drug).
IgE mediated hypersensitivity reactions
Type I reactions are mediated by antigen-specific IgE and the products of tissue mast cells. Most common allergic reactions are type I reactions. In addition, most type I reactions occur against environmental antigens and are therefore allergic. Because of this strong association, many healthcare professionals use the term allergy to indicate only IgE-mediated reactions. However, IgE can contribute to some autoimmune and alloimmune diseases, and many common allergies (e.g., poison ivy) are not mediated by IgE.
What is the most potent mediator of IgG-mediated hypersensitivity?
What are the clinical manifestations of IgE-mediated hypersensitivity?
- The clinical manifestations of type I reactions are attributable mostly to the biologic effects of histamine. The tissues most commonly affected by type I responses contain large numbers of mast cells and are sensitive to the effects of histamine released from them. These tissues are found in the gastrointestinal tract, the skin, and the respiratory tract (Figure 7-10 and Table 7-16).
- Gastrointestinal allergy is caused primarily by allergens that enter through the mouth—usually foods or medicines. Symptoms include vomiting, diarrhea, or abdominal pain. Foods most often implicated in gastrointestinal allergies are milk, chocolate, citrus fruits, eggs, wheat, nuts, peanut butter, and fish. The most common food allergy in adults is a reaction to shellfish, which may initiate an anaphylactic
- A dermal (skin) manifestation of allergic reactions
What are some type I Hypersensitivity reactions?
- Manifestations of allergic reactions as a result of type I hypersensitivity include pruritus, angioedema (swelling caused by exudation), edema of the larynx, urticaria (hives), bronchospasm (constriction of airways in the lungs), hypotension (low blood pressure), and dysrhythmias (irregular heartbeat) because of anaphylactic shock, and gastrointestinal cramping caused by inflammation of the gastrointestinal mucosa. Photographic inserts show a diffuse allergic-like eye and skin reaction on an individual. The skin lesions have raised edges and develop within minutes or hours, with resolution occurring after about 12 hours.
What is the difference between type IV hypersensitivity reactions compared to types I, II and III
- Type IV reactions are mediated by T lymphocytes and do not involve antibody.
- Type IV mechanisms occur through either cytotoxic T lymphocytes (Tc cells) or cytokine-producing Th1 cells. Tc cells attack and destroy cellular targets directly.
Give an example of a type IV hypersensitivity reaction
- Graft rejection
- Skin test for TB
- Poison ivy
WHat is a delayed hypersensitivity skin test?
In 1891 Ehrlich was the first to thoroughly describe a type IV hypersensitivity reaction in the skin, leading to the development of a diagnostic skin test for tuberculosis. The reaction follows an intradermal injection of tuberculin antigen into a suitably sensitized individual and is called a delayed hypersensitivity skin test because of its slow onset—24 to 72 hours to reach maximal intensity. The reaction site is infiltrated with T lymphocytes and macrophages, resulting in a clear hard center (induration) and a reddish surrounding area (erythema).
Development of Allergic Contact Dermatitis
- Chart Reads:
- A, The development of allergy to poison ivy. The first (primary) contact with allergen sensitizes (produces reactive T cells) the individual but does not produce a rash (dermatitis). Secondary contact activates a type IV cell-mediated reaction that causes dermatitis. B, Contact dermatitis caused by a delayed hypersensitivity reaction leading to vesicles and scaling at the sites of contact
Allergic Disease: Bee sting allergy
- Allergies are the most common hypersensitivity diseases. The majority of allergies are type I reactions that lead to annoying symptoms, including rhinitis, sneezing, and other relatively mild reactions. In some individuals, however, these reactions can be excessive and life-threatening (anaphylaxis). Anaphylactic reactions have been described against peanuts and other nuts, shellfish, fish, milk, eggs, and some medications.
- Bee venoms contain a mixture of enzymes and other proteins that may serve as allergens. About 1% of children may have an anaphylactic reaction to bee venom. Within minutes they may develop excessive swelling (edema) at the bee sting site, followed by generalized hives, pruritus, and swelling in areas distal from the sting (e.g., eyes, lips), and other systemic symptoms including flushing, sweating, dizziness, and headache. The most severe symptoms may include gastrointestinal (e.g., stomach cramps, vomiting), respiratory (e.g., tightness in the throat, wheezing, difficulty breathing), and vascular (e.g., low blood pressure, shock) reactions. Severe respiratory and vascular reactions may lead to death.
- For an individual with known bee sting hypersensitivity, life-style changes include avoidance of stinging or biting insects. If a child has experienced a previous anaphylactic reaction, the chance of having another is about 60%. The primary life-threatening symptoms result from contraction of respiratory smooth muscle. Autonomic nervous system mediators, such as epinephrine, bind to specific receptors on smooth muscle and reverse the effects of histamine, resulting in muscle relaxation. Thus most individuals carry self-injectable epinephrine. The administration of antihistamines will have little effect because histamine has already bound H1 receptors and initiated severe bronchial smooth muscle contraction. Long-term protection may be afforded by desensitization in most individuals.
The books explanation of autoimmunity
- It is fairly well established that most autoimmune diseases originate from a genetic predisposition to mount a hypersensitivity reaction to an environmental stimulus.49 Some autoimmune diseases can be familial and attributed to the presence of a very small number of susceptibility genes; affected family members may not all develop the same disease, but several members may have different disorders characterized by a variety of hypersensitivity reactions, including autoimmune and allergic. Although most autoimmune diseases appear as isolated events without a positive family history, susceptibility for developing such diseases appears to be linked to a combination of multiple genes.
- An individual is usually tolerant to his or her own antigens. Tolerance is a state of immunologic control so that the individual does not make a detrimental immune response against his or her own cells and tissues. Autoimmune disease results from a breakdown of this tolerance.
Give an example of a serious autoimmune disease
Systemic lupus erythematosus (SLE) in the most common, complex, and serious of the autoimmune disorders.
ABO Blood system
- The ABO blood group consists of two major carbohydrate antigens, labeled A and B (Figure 7-15), that are expressed on virtually all cells. These are co-dominant so that both A and B can be simultaneously expressed, resulting in an individual having any one of four different blood types. The erythrocytes of persons with blood type A have the type A carbohydrate antigen (i.e., carry the A antigen), those with blood type B carry the B antigen, those with blood type AB carry both A and B antigens, and those of blood type O carry neither the A nor the B antigen. A person with type A blood also has circulating antibodies to the B carbohydrate antigen. If this person receives blood from a type AB or B individual, a severe transfusion reaction occurs, and the transfused erythrocytes are destroyed by agglutination or complement-mediated lysis. Similarly, a type B individual (whose blood contains anti-A antibodies) cannot receive blood from a type A or AB donor. Type O individuals, who have neither antigen but have both anti-A and anti-B antibodies, cannot accept blood from any of the other three types. These naturally occurring antibodies, called isohemagglutinins, are IgM immunoglobulins and are induced early in life against similar antigens expressed on naturally occurring bacteria in the intestinal tract.
- Because individuals with type O blood lack both types of antigens, they are considered universal donors, meaning that anyone can accept their red blood cells. Similarly, type AB individuals are considered universal recipients because they lack both anti-A and anti-B antibodies and can be transfused with any ABO blood type. Agglutination and lysis cause harmful transfusion reactions that can be prevented only by complete and careful ABO matching between donor and recipient.
Rh system (related to blood typing)
- The Rh blood group is a group of antigens expressed only on red blood cells. This is most diverse group of red cell antigens, consisting of at least 45 separate antigens, although only one is considered of major importance: the D antigen. Individuals who express the D antigen on their red cells are Rh-positive, whereas individuals who do not express the D antigen are Rh-negative. When discussing the gene for the Rh antigen, the letter d is used to indicate lack of D. Rh-positive individuals can have either a DD or Dd genotype, whereas Rh-negative individuals have the dd genotype. About 85% of North Americans are Rh-positive. Rh-negative individuals can make an IgG antibody to the D antigen (anti-D) if exposed to Rh-positive erythrocytes.
- A disease called hemolytic disease of the newborn was most commonly caused by IgG anti-D alloantibody produced by Rh-negative mothers against erythrocytes of their Rh-positive fetuses (see Chapter 21). The mother's antibody crossed the placenta and destroyed the red blood cells of the fetus. The occurrence of this particular form of the disease has decreased dramatically because of the use of prophylactic anti-D immunoglobulin (i.e., RhoGAM). By mechanisms that are still not completely understood, administration of anti-D antibody within a few days of exposure to RhD-positive erythrocytes completely prevents sensitization against the D antigen. Because hemolytic disease of the newborn related to the D antigen has been controlled, alloantibodies against the other Rh antigens have become more important. In general, these alloantibodies are associated with a less severe hemolytic disease.
ABO Blood types
This figure shows the relationship of antigens and antibodies associated with the ABO blood groups. The surfaces of erythrocytes of individuals with blood group O have a core carbohydrate that is present on cells of all ABO blood groups (H antigen). The sera of blood group O individuals contain IgM antibodies against both A and B carbohydrates. In individuals of the blood group A, some of the H antigens have been modified into A antigens. The sera of these individuals have IgM antibodies against the B antigen. In individuals with blood group B, some of the H antigens have been modified into B antigens. These individuals have IgM antibodies against the A antigen in their sera. In individuals of the blood group AB, some of the H antigens have been modified into both the A and B antigens. These individuals do not have antibody to either A or B antigens.
This was highlighted
Human Leukocyte Antigens (HLAs). The major histocompatibility complex (MHC) is located on chromosome 6 and contains genes that code for class I antigens, class II antigens, and class III proteins (i.e., complement proteins and cytokines).
The diversity of MHC (major histocompatibility complex) molecules becomes clinically relevant during organ transplantation. The recipient of a transplant can mount an immune response against the foreign MHC antigens on the donor tissue, resulting in rejection. To minimize the chance of tissue rejection, the donor and recipient are often tissue-typed beforehand to identify differences in HLA (human leukocyte antigens) antigens.
Funny we should need to know this!!
Modern society is full of stress. Stress experiences involve daily hassles (e.g., fast-paced scheduling, the pressure to remain in constant contact through social media or cell phones, or both), major life events (e.g., loss of family member, loss of job), abuse, and trauma. Americans have become accustomed to an accelerated way of life with chronic stress by adopting behaviors (e.g., smoking, drinking, drug abuse, sleep disturbances) that may result in the so-called stress-related disorders. In general, stress begins with a stimulus that the brain perceives as stressful and in turn promotes adaptation- and survival-related physiologic responses. These responses can become dysregulated and cause pathophysiologic consequences. Another way to think about this is that acute stress is considered to enhance immunity whereas chronic stress is now considered to suppress immunity.
Historical background about GAS
- Walter B Cannon discovered the biologic syndrome of stress.
- He repeatedly found that three structural changes occurred: (1) enlargement of the cortex of the adrenal gland, (2) atrophy of the thymus gland and other lymphoid structures, and (3) development of bleeding ulcers in the stomach and duodenal lining. Selye soon discovered that these manifestations were not specific to injected ovarian extracts but also occurred after exposure of the rats to other noxious stimuli, such as cold, surgical injury, and restraint. He called these stimuli stressors. Selye concluded that this triad or syndrome of manifestations represented a nonspecific response to noxious stimuli, naming it the general adaptation syndrome (GAS).
Three stages of GAS
- (1) the alarm stage or reaction, in which the central nervous system (CNS) is aroused and the body's defenses are mobilized (e.g., “fight or flight”); (2) the stage of resistance or adaptation, during which mobilization contributes to “fight or flight;” and (3) the stage of exhaustion, where continuous stress causes the progressive breakdown of compensatory mechanisms (acquired adaptations) and homeostasis. Exhaustion marks the onset of certain diseases (diseases of adaptation).
- Interactions among the sympathetic branch of the autonomic nervous system (ANS) and the hypothalamus, pituitary, and adrenal glands produce the nonspecific physiologic
Describe the alarm reaction
The Alarm Reaction. The alarm reaction includes increased secretion of glucocorticoids (cortisol) by the adrenal cortex and increased secretion of epinephrine and small amounts of norepinephrine from the adrenal medulla.
Hypothalamic-Putuitary Adrenal (HPA) Axis
- Hypothalamic-Pituitary-Adrenal (HPA) Axis. The response to stress begins in the brain. The hypothalamus is the control center in the brain for many hormones including corticotropin-releasing hormone (CRH).
What are catecholamines?
- Circulating catecholamines essentially mimic direct sympathetic stimulation. Catecholamines cannot cross the blood-brain barrier and are synthesized locally in the brain. The physiologic effects of the catecholamines on organs and tissues are summarized in Table 8-2. Norepinephrine regulates blood pressure, promotes arousal, and increases vigilance, anxiety, and other protective emotional responses.
- See figure 8-2
What are genes?
Genes are composed of sequences of DNA. By serving as the blueprints of proteins in the body, genes ultimately influence all aspects of body structure and function. Estimates suggest that there are approximately 20,000 to 25,000 genes. An error in one of these genes often leads to a recognizable genetic disease.
What are the different bases in DNA?
Genes are composed of DNA, which has three basic components: the five-carbon monosaccharide deoxyribose; a phosphate molecule; and four types of nitrogenous bases. Two of the bases, cytosine and thymine, are single carbon-nitrogen rings called pyrimidines. The other two bases, adenine and guanine, are double carbon-nitrogen rings called purines. The four bases are commonly represented by their first letters: A, C, T, and G.
Describe the double helix?
Watson and Crick demonstrated how molecules are physically assembled as DNA, proposing the double-helix model, in which DNA appears like a twisted ladder with chemical bonds as its rungs. The two sides of the ladder consist of deoxyribose and phosphate molecules, united by strong phosphodiester bonds. Projecting from each side of the ladder, at regular intervals, are the nitrogenous bases. The base projecting from one side is bound to the base projecting from the other by a weak hydrogen bond. Therefore the nitrogenous bases form the rungs of the ladder; adenine pairs with thymine, and guanine pairs with cytosine.
DNA as the genetic code
DNA directs the synthesis of all the body's proteins. Proteins are composed of one or more polypeptides (intermediate protein compounds), which are in turn consist of sequences of amino acids. The body contains 20 different types of amino acids
What is a mutation?
A mutation is any inherited alteration of genetic material. Mutations may cause disease or be subtle, silent substitutions that do not change amino acids
RNA vs DNA
DNA is formed and replicated in the cell nucleus, but protein synthesis takes place in the cytoplasm. The DNA code is transported from nucleus to cytoplasm, and subsequent protein is formed through two basic processes: transcription and translation. These processes are mediated by ribonucleic acid (RNA), which is chemically similar to DNA except that the sugar molecule is ribose rather than deoxyribose, and uracil rather than thymine is one of the four bases. The other bases of RNA, as in DNA, are adenine, cytosine, and guanine. Uracil is structurally similar to thymine, so it also can pair with adenine. Whereas DNA usually occurs as a double strand, RNA usually occurs as a single strand.
- In transcription, RNA is synthesized from a DNA template, forming messenger RNA (mRNA). RNA polymerase binds to a promoter site, a sequence of DNA that specifies the beginning of a gene. RNA polymerase then separates a portion of the DNA, exposing unattached DNA bases. One DNA strand then provides the template for the sequence of mRNA nucleotides.
- The sequence of bases in the mRNA is thus complementary to the template strand, and except for the presence of uracil instead of thymine, the mRNA sequence is identical to the other DNA strand. Transcription continues until a termination sequence, codons that act as signals for the termination of protein synthesis, is reached. Then the RNA polymerase detaches from the DNA, and the transcribed mRNA is freed to move out of the nucleus and into the cytoplasm
Information on Down Syndrome
- The best-known example of aneuploidy in an autosome is trisomy of the twenty-first chromosome, which causes Down syndrome (named after J. Langdon Down, who first described the disease in 1866). Down syndrome is seen in approximately 1 in 800 to 1 in 1000 live births
- The risk of having a child with Down syndrome increases greatly with maternal age.
- women younger than 30 years have a risk ranging from about 1 in 1000 births to 1 in 2000 births. The risk begins to rise substantially after 35 years of age, and it reaches 3% to 5% for women older than 45 years. This dramatic increase in risk is caused by the age of maternal egg cells, which are held in an arrested state of prophase I from the time they are formed in the female embryo until they are shed in ovulation. Thus an egg cell formed by a 45-year-old woman is itself 45 years old. This long suspended state may allow defects to accumulate in the cellular proteins responsible for meiosis, leading to nondisjunction. The risk of Down syndrome, as well as other trisomies, does not increase with paternal age.
Differentiate between phenotype and genotype
The composition of genes at a given locus is known as the genotype. The outward appearance of an individual, which is the result of both genotype and environment, is the phenotype. For example, an infant who is born with an inability to metabolize the amino acid phenylalanine has the single-gene disorder known as phenylketonuria (PKU) and thus has the PKU genotype.
Dominances and Recessiveness
In many loci, the effects of one allele mask those of another when the two are found together in a heterozygote. The allele whose effects are observable is said to be dominant. The allele whose effects are hidden is said to be recessive (from the Latin root for “hiding”). Traditionally, for loci having two alleles, the dominant allele is denoted by an uppercase letter and the recessive allele is denoted by a lowercase letter. When one allele is dominant over another, the heterozygote genotype Aa has the same phenotype as the dominant homozygote AA. For the recessive allele to be expressed, it must exist in the homozygote form, aa. When the heterozygote is distinguishable from both homozygotes, the locus is said to exhibit codominance.
Describe a carrier of a diseased gene
A carrier is an individual who has a disease gene but is phenotypically normal. Many genes for a recessive disease occur in heterozygotes who carry one copy of the gene but do not express the disease. When recessive genes are lethal in the homozygous state, they are eliminated from the population when they occur in homozygotes. By “hiding” in carriers, however, recessive genes for diseases are passed on to the next generation.
Transmission of genetic diseases
- The pattern in which a genetic disease is inherited through generations is termed the mode of inheritance. Knowing the mode of inheritance can reveal much about the disease gene itself, and members of families with the disease can be given reliable genetic counseling.
- Gregor Mendel systematically studied modes of inheritance and formulated two basic laws of inheritance. His principle of segregation states that homologous genes separate from one another during reproduction and that each reproductive cell carries only one homologous gene. Mendel's second law, the principle of independent assortment, states that the hereditary transmission of one gene does not affect the transmission of another.
Sex linked (X and Y Chromosomes)
- Some genetic conditions are caused by mutations in genes located on the sex chromosomes, and this mode of inheritance is termed sex linked. Only a few diseases are known to be inherited as X-linked dominant or Y chromosome traits, so only the more common X-linked recessive diseases are discussed here.
- Because females receive two X chromosomes, one from the father and one from the mother, they can be homozygous for a disease allele at a given locus, homozygous for the normal allele at the locus, or heterozygous. Males, having only one X chromosome, are hemizygous for genes on this chromosome. If a male inherits a recessive disease gene on the X chromosome, he will be affected by the disease because the Y chromosome does not carry a normal allele to counteract the effects of the disease gene. Because a single copy of an X-linked recessive gene will cause disease in a male, whereas two copies are required for disease expression in females, more males are affected by X-linked recessive diseases than are females.
Describe X inactivation
In the late 1950s Mary Lyon proposed that one X chromosome in the somatic cells of females is permanently inactivated, a process termed X inactivation. This proposal, the Lyon hypothesis, explains why most gene products coded by the X chromosome are present in equal amounts in males and females, even though males have only one X chromosome and females have two X chromosomes.
The process of sexual differentiation, in which the embryonic gonads become either testes or ovaries, begins during the sixth week of gestation. A key principle of mammalian sex determination is that one copy of the Y chromosome is sufficient to initiate the process of gonadal differentiation that produces a male fetus. The number of X chromosomes does not alter this process. For example, an individual with two X chromosomes and one Y chromosome in each cell is still phenotypically a male. Thus the Y chromosome contains a gene that begins the process of male gonadal development.
Human Gene Map/the Human Genome Project
- The major goals of the Human Genome Project were to find the locations of all human genes (the “gene map”) and to determine the entire human DNA sequence. These goals have now been accomplished and the genes responsible for most mendelian conditions have been identified (Figure 2-31).1,16,17 This has greatly increased our understanding of the mechanisms that underlie many diseases, such as retinoblastoma, cystic fibrosis, neurofibromatosis, and Huntington disease. It also has led to more accurate diagnosis of these conditions, and in some cases more effective treatment.
- DNA sequencing has become much less expensive and more efficient in recent years. Consequently, dozens of individuals have now been completely sequenced, leading in some cases to the identification of disease-causing genes
- a reversible, structural, or functional response both to normal or physiologic conditions and to adverse or pathologic conditions.
- For example, the uterus adapts to pregnancy—a normal physiologic state—by enlarging.
Cellular adaptation overview
Cells adapt to their environment to escape and protect themselves from injury. An adapted cell is neither normal nor injured—its condition lies somewhere between these two states. Cellular adaptations, however, are a common and central part of many disease states. In the early stages of a successful adaptive response, cells may have enhanced function; thus it is hard to know whether the response is pathologic or an extreme adaptation to an excessive functional demand. The most significant adaptive changes in cells include atrophy (decrease in cell size), hypertrophy (increase in cell size), hyperplasia (increase in cell number), and metaplasia (reversible replacement of one mature cell type by another less mature cell type). Dysplasia (deranged cellular growth) is not considered a true cellular adaptation but rather an atypical hyperplasia.
- Increase in cell number
- Hyperplasia, as a response to injury, occurs when the injury has been severe and prolonged enough to have caused cell death. Loss of epithelial cells and cells of the liver and kidney triggers deoxyribonucleic acid (DNA) synthesis and mitotic division. Increased cell growth is a multistep process involving the production of growth factors, which stimulate the remaining cells to synthesize new cell components and, ultimately, to divide.
- increase in cell size
- The cells of the heart and kidneys are particularly prone to enlargement. The increased cellular size is associated with an increased accumulation of protein in the cellular components (plasma membrane, endoplasmic reticulum, myofilaments, mitochondria) and not with an increase in cellular fluid. Hypertrophy can be physiologic or pathologic and is caused by specific hormone stimulation or by increased functional demand.
- Ex: Stretch, growth factors, hormones and vasoactive agents. When a diseased kidney is removed, the remaining kidney adapts to the increased workload with an increase in both the size and the number of cells.
- decrease in cell size
- The atrophic muscle cell contains less endoplasmic reticulum and fewer mitochondria and myofilaments (part of the muscle fiber that controls contraction) than found in the normal cell. In muscular atrophy caused by nerve loss, oxygen consumption and amino acid uptake are immediately reduced. The biochemical changes of atrophy are just beginning to be understood. The mechanisms probably include decreased protein synthesis, increased protein catabolism, or both.
- reversible replacement of one mature cell type by another less mature cell type, sometimes less differentiated, cell type.
- It is thought to develop from a reprogramming of stem cells that exist on most epithelia or of undifferentiated mesenchymal (tissue from embryonic mesoderm) cells present in connective tissue. These precursor cells mature along a new pathway because of signals generated by growth factors in the cell's environment. The best example of metaplasia is replacement of normal columnar ciliated epithelial cells of the bronchial (airway) lining by stratified squamous epithelial cells
- deranged cellular growth-refers to abnormal changes in the size, shape, and organization of mature cells
- Dysplasia is not considered a true adaptive process but is related to hyperplasia and is often called atypical hyperplasia. Dysplastic changes often are encountered in epithelial tissue of the cervix and respiratory tract, where they are strongly associated with common neoplastic growths and often are found adjacent to cancerous cells. Importantly, however, the term dysplasia does not indicate cancer and may not progress to cancer.
Learn figure 3-1
Most diseases begin with cell injury. Cellular injury occurs if the cell is unable to maintain homeostasis—a normal or adaptive steady state—in the face of injurious stimuli. Injured cells may recover (reversible injury) or die (irreversible injury). Injurious stimuli include chemical agents, lack of sufficient oxygen (hypoxia), free radicals, infectious agents, physical and mechanical factors, immunologic reactions, genetic factors, and nutritional imbalances.
Health Alert: Unintentional Injury Errors in Healthcare-Lengthy but important
- Errors in healthcare are an unintended event; no matter how trivial or commonplace, they are errors that could or did harm individuals. Medical errors are one of the leading causes of death and injury in the United States. Medical errors occur because the medical plan fails or is the wrong plan. A 1999 report by the Institute of Medicine (IOM) estimates that as many as 44,000 to 98,000 people in the United States die in hospitals each year as the result of medical errors. These data mean that more people die from medical errors than from motor vehicle accidents, breast cancer, or AIDS. Although these statistics have been challenged, the IOM report noted that many of the errors in healthcare result from a culture and system that are fragmented and solving this major problem will require extensive foundation or infrastructure building. Errors involve medicines, surgery, diagnosis, equipment, and laboratory reports. They can occur anywhere in the healthcare system, including hospitals, clinics, outpatient surgery centers, physicians’ and nurse practitioners’ offices, pharmacies, and an individual's home. Errors can happen during the most routine of plans, such as when an individual is prescribed a low-salt diet and is given a high-salt meal. Research indicated that most mistakes were not due to clinicians’ negligence but rather from inherent shortcomings in the healthcare system. Yet errors can occur when clinicians and their clients have trouble communicating.
- Although the literature about errors in healthcare has grown substantially over the last decade, we do not yet have a compelling analysis of the epidemiology of error. More is known about errors in hospitals than in other healthcare delivery settings. Medication-related error has been studied for several reasons: (1) it is the most common type of error, (2) substantial numbers of people are affected, and (3) it accounts for a large increase in healthcare costs. Medication errors are methodologically easier to study because the drug prescribing process provides documentation of medical decisions, administration of drugs is recorded, supplying drugs are documented, and deaths attributable to medication errors are recorded on death certificates. According to the Agency for Healthcare Research and Quality (AHRQ) the rate for potential adverse drug events was three times higher in children and much higher for babies in neonatal intensive care units. New data show bar-code technology with an electronic medication administration record (eMAR) substantially reduces transcription and medication administration errors. This technology also reduces potential drug-related adverse events. Bar-code eMAR is a combination of technologies that ensures the correct medication is administered to the right patient at the right dose and time. When nurses use these technologies, medication orders appear electronically in the individual's chart after pharmacist approval. Electronic alerts are sent to nurses if the medication is overdue and before administering the medication. Nurses are required to scan the bar code on the individual's wristband and then on the medication. A warning is issued if the bar codes do not match or it is the wrong time for administration of the medication.
- Other errors, in addition to medication errors, include surgical injuries and wrong-site surgery; preventable suicides, restraint-related injuries, or death; hospital-acquired or other treatment-related infections; falls; burns; pressure ulcers; and mistaken identity. Studies of errors outside the hospital have begun.
- The IOM report has galvanized a national movement to improve client safety and eliminate healthcare errors. “Errors and excess mortality can be eliminated but only if concern and attention is shifted away from individuals and toward the error-prone systems in which clinicians work” (Leape, 2000).
Cellular death eventually leads to cellular dissolution, or necrosis. Necrosis is the sum of cellular changes after local cell death and the process of cellular self-digestion, known as autodigestion or autolysis
Apoptosis is an active process of cellular self-destruction called programmed cell death and is implicated in both normal and pathologic tissue changes. Cells need to die; otherwise, endless proliferation would lead to gigantic bodies. The average adult may create 10 billion new cells every day—and destroy the same number.
When does apoptosis normally occur
- Normal physiologic death by apoptosis occurs during the following processes:
- • Embryogenesis
- • Involution of hormone-dependent tissue after hormone withdrawal (such as involution of the lactating breast after weaning)
- • Cell loss in proliferating cell populations (such as immature lymphocytes in the bone marrow or thymus that do not express appropriate receptors)
- • Elimination of possibly harmful lymphocytes that may be self-reactive and cause cell death after performing useful functions (for example, neutrophils after an acute inflammatory reaction)